Role of innate lymphoid cell in gastric carcinogenesis

• Project/Area Number: 17K09359
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka City University
• Principal Investigator: OTANI Koji 大阪市立大学, 大学院医学研究科, 講師 (30597555)
• Co-Investigator(Kenkyū-buntansha): 灘谷 祐二 大阪市立大学, 大学院医学研究科, 講師 (00634007) ; 谷川 徹也 大阪市立大学, 大学院医学研究科, 准教授 (70423879) ; 渡邉 俊雄 大阪市立大学, 大学院医学研究科, 准教授 (50336773) ; 藤原 靖弘 大阪市立大学, 大学院医学研究科, 教授 (40285292)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自然リンパ球 / 胃癌 / IL-17 / 消化器内科

Outline of Final Research Achievements

The presence of innate lymphoid cell (ILC) has been revealed in innate immunity, and its role in various diseases attracts attention. It is guessed that ILC is also deeply involved in gastric carcinogenesis, but the expression of ILC and its producing cytokines is unknown. Therefore, we aimed to elucidate the expression of ILC3 population, the inductive mechanism of interleukin (IL)-17 and IL-22, and the mutual regulation with the other ILC groups and the significance in the tumor immunity of gastric cancer. As a result, it was suggested that IL-17 and IL-22 produced by ILC3 promote gastric carcinogenesis through the inhibition of ILC1 having anti-tumor activity and interferon-γ produced by ILC1.

Academic Significance and Societal Importance of the Research Achievements

自然リンパ球 (ILC) と同じ自然免疫応答を担うナチュラルキラー細胞はがん細胞に対して非常に強い殺傷能をもち、ILC1にも強い抗腫瘍活性があると考えられる。今回ILC3にILC1分化の抑制を介した腫瘍形成促進作用があることが明らかになったことにより、ILC1の活性化に加えてILC3の活性を抑制することで今後のがん免疫治療や、サイトカインや転写因子を標的とした分子標的治療が大きく進展することが期待される。